2. Academic Validation
  3. Laurinterol from Laurencia johnstonii eliminates Naegleria fowleri triggering PCD by inhibition of ATPases

Laurinterol from Laurencia johnstonii eliminates Naegleria fowleri triggering PCD by inhibition of ATPases

  • Sci Rep. 2020 Oct 20;10(1):17731. doi: 10.1038/s41598-020-74729-y.
Iñigo Arberas-Jiménez 1 2 3,  Sara García-Davis 4,  Aitor Rizo-Liendo 1 2,  Ines Sifaoui 1 2 3 5,  María Reyes-Batlle 1 2 3 5,  Olfa Chiboub 1 5,  Rubén L Rodríguez-Expósito 1 2 3,  Ana R Díaz-Marrero 4,  José E Piñero 6 7 8,  José J Fernández 9 10,  Jacob Lorenzo-Morales 11 12 13
Affiliations

Affiliations

  • 1 Instituto Universitario de Enfermedades Tropicales y Salud Pública de Canarias (IUETSPC), Universidad de La Laguna (ULL), Avda. Astrofísico F. Sánchez, s/n, 38203, La Laguna, Tenerife, Spain.
  • 2 Departamento de Obstetricia y Ginecología, Pediatría, Medicina Preventiva y Salud Pública, Toxicología, Medicina Legal Y Forense Y Parasitología, Universidad de La Laguna (ULL), Avda. Astrofísico F. Sánchez, s/n, 38206, La Laguna, Tenerife, Spain.
  • 3 Red de Investigación Colaborativa en Enfermedades Tropicales (RICET), Madrid, Spain.
  • 4 Instituto Universitario de Bio-Orgánica Antonio González (IUBO AG), Universidad de La Laguna (ULL), Avda. Astrofísico F. Sánchez, 2, 38206, La Laguna, Tenerife, Spain.
  • 5 Laboratoire Matériaux-Molécules Et Applications, La Marsa, University of Carthage, Tunis, Tunisia.
  • 6 Instituto Universitario de Enfermedades Tropicales y Salud Pública de Canarias (IUETSPC), Universidad de La Laguna (ULL), Avda. Astrofísico F. Sánchez, s/n, 38203, La Laguna, Tenerife, Spain. jpinero@ull.edu.es.
  • 7 Departamento de Obstetricia y Ginecología, Pediatría, Medicina Preventiva y Salud Pública, Toxicología, Medicina Legal Y Forense Y Parasitología, Universidad de La Laguna (ULL), Avda. Astrofísico F. Sánchez, s/n, 38206, La Laguna, Tenerife, Spain. jpinero@ull.edu.es.
  • 8 Red de Investigación Colaborativa en Enfermedades Tropicales (RICET), Madrid, Spain. jpinero@ull.edu.es.
  • 9 Instituto Universitario de Bio-Orgánica Antonio González (IUBO AG), Universidad de La Laguna (ULL), Avda. Astrofísico F. Sánchez, 2, 38206, La Laguna, Tenerife, Spain. jjfercas@ull.edu.es.
  • 10 Departamento de Química Orgánica, Universidad de La Laguna (ULL), Avda. Astrofísico F. Sánchez, s/n, 38206, La Laguna, Tenerife, Spain. jjfercas@ull.edu.es.
  • 11 Instituto Universitario de Enfermedades Tropicales y Salud Pública de Canarias (IUETSPC), Universidad de La Laguna (ULL), Avda. Astrofísico F. Sánchez, s/n, 38203, La Laguna, Tenerife, Spain. jmlorenz@ull.edu.es.
  • 12 Departamento de Obstetricia y Ginecología, Pediatría, Medicina Preventiva y Salud Pública, Toxicología, Medicina Legal Y Forense Y Parasitología, Universidad de La Laguna (ULL), Avda. Astrofísico F. Sánchez, s/n, 38206, La Laguna, Tenerife, Spain. jmlorenz@ull.edu.es.
  • 13 Red de Investigación Colaborativa en Enfermedades Tropicales (RICET), Madrid, Spain. jmlorenz@ull.edu.es.
PMID: 33082417 DOI: 10.1038/s41598-020-74729-y
Abstract

Primary amoebic encephalitis (PAM) is a lethal disease caused by the opportunistic pathogen, Naegleria fowleri. This amoebic species is able to live freely in warm aquatic habitats and to infect children and young adults when they perform risk activities in these water bodies such as swimming or splashing. Besides the need to increase awareness of PAM which will allow an early diagnosis, the development of fully effective therapeutic agents is needed. Current treatment options are amphotericin B and miltefosine which are not fully effective and also present toxicity issues. In this study, the in vitro activity of various Sesquiterpenes isolated from the red alga Laurencia johnstonii were tested against the trophozoite stage of a strain of Naegleria fowleri. Moreover, the induced effects (apoptotic cell death) of the most active compound, laurinterol (1), was evaluated by measuring DNA condensation, damages at the mitochondrial level, cell membrane disruption and production of Reactive Oxygen Species (ROS). The obtained results demonstrated that laurinterol was able to eliminate the amoebae at concentrations of 13.42 ± 2.57 µM and also to induced programmed cell death (PCD) in the treated amoebae. Moreover, since ATP levels were highly affected and laurinterol has been previously reported as an inhibitor of the Na+/K+-ATPase sodium-potassium ion pump, comparison with known inhibitors of ATPases were carried out. Our results points out that laurinterol was able to inhibit ENA ATPase pump at concentrations 100 times lower than furosemide.

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